Abstract
PURPOSE: Sphingosine-1-phosphate (S1P) plays a pivotal role in cells as a bioactive lipid mediator, with emerging evidence suggesting that it may play a role in retinal ganglion cell survival, axonal growth, retinal pigment epithelium (RPE) barrier function, and photoreceptor function. While previous studies have documented associated ophthalmic effects such as fingolimod-associated macular edema, the specific impact of S1P receptor modulators on inner and outer retinal layer thicknesses requires further elucidation. DESIGN: Retrospective case series. SUBJECTS: A total of 44 patients (86 eyes) with multiple sclerosis (MS) treated with fingolimod between 2011 and 2023 at the John L. Trotter Multiple Sclerosis Center at Washington University in St. Louis. METHODS: Eligible participants were those with baseline and follow-up OCT images conducted at or prior to S1P initiation and at the most recent visit. The peripapillary retinal nerve fiber layer (pRNFL), ganglion cell layer (GCL), central subfield thickness (CST), macular volume (MV), RPE, and photoreceptor thickness were determined through OCT segmentation. Generalized estimating equations were constructed incorporating relevant covariates. MAIN OUTCOME MEASURES: Annualized rate of change of specified retinal layer thickness. RESULTS: The mean age was 49.4 ± 10.8 years and time between baseline and follow-up OCTs ranged from 2 months to 6.4 years with a median of 1 year, interquartile range 0.42 to 2.33. The annualized rate of change of pRNFL and CST were 0.022 [-0.363, 0.406] μm/year, and -1.37 [-3.11, 0.38] μm/year, whereas GCL and MV showed significant thinning of -0.231 [-0.430, -0.032] μm/year and -0.024 [-0.047, -0.001] mm3/year, respectively. Retinal pigment epithelium and photoreceptor layer thickness remained largely stable over time at 0.070 [-0.140, 0.280] μm/year and 0.673 [-0.218, 1.561] μm/year, respectively. CONCLUSIONS: Patients with MS on S1P modulators exhibited significant GCL and MV thinning with outer retina layer thickness preservation, providing insight into the potential retinal effects of S1P modulation in the setting of MS-related neurodegeneration. Prospective studies with standardized imaging intervals and appropriate controls are needed to distinguish the specific retinal effect of S1P modulation from MS neurodegeneration and enable more precise OCT interpretation of the retina in monitoring MS disease progression. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.